The expected survival of patients with metastatic gastric cancer is less than one year. Very few new drugs have been approved for this disease in the past decade. The phase II KEYNOTE-059 is one of the largest studies to investigate immunotherapy in recurrent or metastatic gastric cancer.

The study included three cohorts: 1) 259 patients with metastatic gastric cancer who received the programmed death 1 (PD-1) inhibitor pembrolizumab alone, after pretreatment with two or more lines of chemotherapy; 2) 25 patients with newly diagnosed metastatic gastric cancer who received a combination of pembrolizumab and chemotherapy; 3) 31 patients with newly diagnosed metastatic gastric cancer who received pembrolizumab alone.

The primary endpoints were safety (all three cohorts) and objective response rate (cohorts one and three).

After a median follow-up of six months, the investigators found an overall objective response rate of 12% with pembrolizumab alone in the pretreated patients (cohort one). Patients who expressed programmed death-ligand 1 (PD-L1) were more likely to respond than those who did not, with objective response rates of 16% and 6%, respectively. Many of the responses were durable. Grade 3 to 5 treatment-related adverse events occurred in 18% of patients in cohort one and 3% had to discontinue treatment as a result.

Lead author Dr Zev Wainberg, co-director of the Gastrointestinal Oncology Programme, UCLA, Los Angeles, US, said: “The data shows that the tumours were sufficiently shrunk to warrant a response, particularly in those patients who had PD-L1 expression, and the drug was safe. The expected response rate in these heavily pretreated patients was close to zero so the findings are encouraging.”

In patients with newly diagnosed metastatic cancer, both the combination therapy (cohort two) and pembrolizumab alone (cohort three) were safe and showed some promising activity. “These results have set the stage for a larger follow-up study which is already enrolling patients,” said Wainberg.

He concluded: “We hope these results, in combination with evidence from ongoing randomised trials, will support the regulatory approval of pembrolizumab in metastatic gastric cancer.”

Commenting on the results for ESMO, Dr Ian Chau, consultant medical oncologist, Royal Marsden Hospital, London and Surrey, UK, said: “There is currently no standard of care for metastatic gastric cancer treated in the third line or beyond. The KEYNOTE-059 cohort 1 results confirm that the efficacy previously reported for the PD-1 inhibitor nivolumab in patients from East Asia in the ONO-4538 randomised trial can be applied to Western populations.”

“The likelihood is that pembrolizumab will become a standard treatment option in this setting in the near future,” he added.

Chau cautioned that while the toxicity profile of pembrolizumab looked quite favourable in KEYNOTE-059, it could be that patients had not been treated long enough to experience side effects. He said: “Unlike with chemotherapy, toxicities from immunotherapy tend to occur later on. We need to await longer-term results from an ongoing clinical trial in an earlier line of treatment to know the full impact of this drug in metastatic gastric cancer.”

He concluded: “Further research should focus on refining the PD-L1 biomarker and searching for better biomarkers to tell us who benefits from these therapies. We also need more information about quality of life which should be provided by ongoing studies.”

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Notes to Editors

Please make sure to use the official name of the meeting in your reports: ESMO 2017 Congress

This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .

ESMO is the leading professional organisation for medical oncology. With 16,000 members representing oncology professionals from over 130 countries worldwide, ESMO is the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.

New data confirms superiority of docetaxel based triplet therapy in gastric cancer

ESMO PRESS RELEASE LUGANO-MADRID, 8 September, 2017 – The superiority of docetaxel based triplet therapy over standard care in patients with resectable oesophago-gastric cancer has been confirmed in late-breaking results from the FLOT4 trial presented at the ESMO 2017 Congress in Madrid. (1)

Survival in resectable oesophago-gastric cancer is poor. Five-year overall survival is around 25% with surgery, and is increased to 36% by adding a perioperative regimen of epirubicin, cisplatin, and infused fluorouracil (ECF). (2) Phase II studies have shown encouraging pathological response rates with perioperative docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT).

Today researchers reveal the results of multivariate, subgroup and sensitivity analyses for the first time. The relative effect of FLOT was observed in all subgroups, including the elderly and signet cell tumours, and was particularly pronounced in Siewert type 1 oesophageal tumours (hazard ratio [HR], 0.60), Barrett tumours (HR, 0.62), small tumours (HR, 0.66) and nodal negative tumours (HR, 0.64).

Lead author Professor Salah-Eddin Al-Batran, director, Institute of Clinical Cancer Research, UCT-University Cancer Centre, Krankenhaus Nordwest, Frankfurt, Germany, said: “These new analyses confirm the superiority of FLOT, which is the new standard of care in the perioperative treatment of patients with resectable gastric or gastroesophageal junction adenocarcinoma.”

He concluded: “Some oncologists believe that patients with small tumours and those with signet cell cancer should not be treated preoperatively. The results of the FLOT4 trial contradict this and show that these patients do benefit.”

Commenting for ESMO, Professor Michel Ducreux, head, Gastrointestinal Oncology Unit, Gustave Roussy, Villejuif, France, said: “The triplet regimen used in the FLOT4 trial was developed to improve the results of ECF. It decreased toxicity by replacing epirubicin with low-dose docetaxel, and using oxaliplatin instead of cisplatin. FLOT is also more convenient to use, with one 24-hour infusion every two weeks rather than continuous infusion of fluorouracil in the ECF protocol.”

“The results show that FLOT is clearly the new standard of care,” continued Ducreux. “The new analysis presented at the ESMO 2017 Congress shows that the advantage of the FLOT regimen was seen across all subgroups, including those with a very poor prognosis such as the elderly and patients with signet cell tumours.”

He concluded: “FLOT will be the best backbone of chemotherapy that we can use in this setting. A step forward would be to try to improve the results by adding targeted therapies or immune checkpoint inhibitors. It would also be interesting to know if the FLOT regimen shows different levels of effectiveness in the four molecular biological subgroups of gastric cancer.”

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Notes to Editors

Please make sure to use the official name of the meeting in your reports: ESMO 2017 Congress

This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .

ESMO is the leading professional organisation for medical oncology. With 16,000 members representing oncology professionals from over 130 countries worldwide, ESMO is the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.

Background: FLOT4 is the first study to show improvement of outcome over another well-established bimodality therapy in patients with esophagogastric cancer. To consolidate initial results, we performed multivariate, subgroup and sensitivity analyses.

Conclusions: Updated analysis confirmed the superiority of FLOT. Pts derived benefit from FLOT even if they were old (>=70), had small tumors, a nodal negative status, or a signet cell component. The presence of one of these factors should no longer be a reason for not considering perioperative therapy in daily practice.

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